Acute leukemia is a disease of the leukocytes and their precursors. It is characterized by the appearance of immature, abnormal cells in the bone marrow and peripheral blood and frequently in the liver, spleen, lymph nodes, and other parenchymatous organs. The clinical picture is marked by the effects of anemia, which is usually severe (fatigue, malaise), an absence of functioning granulocytes (proneness to infection and inflammation), and thrombocytopenia (hemorrhagic diathesis). The spleen and liver usually are moderately enlarged, while enlarged lymph nodes are seen mainly in the pediatric lymphoblastic leukemias. Fever and a very high ESR complete the picture. Leukocyte counts vary greatly in the acute leukemias. About one-fourth to one-third of cases begin with a low white blood count (sub- or aleukemic leukemia), while about half show some degree of leukocytosis. Mature granulocytes may still be found in the peripheral blood in addition to abnormal forms. The coexistence of immature and mature cell forms is termed "hiatus leucaemicus." The leukocytopenic forms are the most difficult to differentiate from aplastic anemias, pancytopenias, and the myelodysplastic syndromes. Bone marrow aspiration is usually necessary to establish a diagnosis. Aspirated marrow is found to be permeated by abnormal cells (paramyeloblasts, paraleukoblasts, nonclassifiable cells (N. C. ), leukemic cells, blasts, etc.) with little or no evidence of normal hematopoiesis.

The acute leukemias are classified according to morphologic, cytochemical, and immunologic criteria (Table 1). The FAB (French-American-British) classification system has become very widely adopted (Benett et al.1976). Besides cytochemical methods (Table 2), immunologic procedures have proved very useful for classifying the acute leukemias and especially for the differentiation of ALL and its subgroups.

Its clinical manifestations and course are basically identical to those of acute leukemia. Besides abnormal granulocytopoietic cells, the peripheral blood (Fig. 23d) contains numerous erythroid precursors which show conspicuous morphologic anomalies (megaloblastic and megaloblastoid cell forms) and are called "paraerythroblasts." These changes are even more impressive in the bone marrow (Figs. 21-23) where numerous karyorrhectic figures and abnormal mitoses are seen in the hyperplastic erythropoiesis. Differentiation from pernicious anemia can be problematic, although the erythroblasts of erythroleukemia are distinguished cytochemically by their high PAS activity (Fig. 23c).

Acute eosinophilic leukemia is diagnosed by examination of the bone marrow, since eosinophils usually are not increased in the peripheral blood. The predominant marrow cells are abnormal eosinophils (immature, pleomorphic forms, some with coarse, dark-blue granules, cytoplasmic vacuoles, distinct nucleoli). Diagnosis relies on the cytochemical detection of naphthol-AS-D-chloracetate esterase in the granules. Auer rods are unusual.

Acute basophilic leukemia is evidenced by an extreme increase in the basophilic granulated cells of granulocytopoiesis. The granules are very atypical (large, coarse, hyperchromic), and Auer rods may be present The diagnosis is confirmed by the metachromatic reaction to toluidine blue in the cells.

Four forms are recognized (after Quattrin 1978):

basophilic blast crises in CML

promyelocytic basophilic type

histiobasophilic type

basophilic-eosinophilic type

It is very difficult to establish a diagnosis of acute megakaryoblastic leukemia, designated M7 in the FAB classification of acute leukemias (Benett et al. 1985). The blast cells in the peripheral blood and bone marrow present a variety of morphologies. They may appear as small cells with a narrow cytoplasmic border and dense chromatin, resembling lymphoblasts (L1), or they may resemble L2 cells with or without granules. The nuclei are round, finely reticular, and have one to three prominent nucleoli. The cells vary greatly in size and may be two to three times larger than normal lymphocytes. Sometimes one finds cytoplasmic vesicles or differentiated megakaryocytes with adjacent platelets or bare nuclei nested in clusters of platelets. Occasional megakaryocytic nuclei are found in the peripheral blood. It is often difficult to obtain a bone marrow specimen by aspiration, and marrow biopsy is usually indicated. Cytochemical methods may contribute to the diagnosis. The Sudan black and peroxidase reaction are negative. The monocytes can be a source of confusion. Often they are positive for alpha-napthylesterase and naphthyl-ASD-acetate esterase, in which case these enzymes canbe inhibited by fluoride. While the monocytes usually show a diffuse positivity for these esterase enzymes, the reaction in megakaryoblasts tends to be localized. PAS and acid phosphatase positivity are also localized. A platelet peroxidase occuring on a nuclear membrane and in the endoplasmic reticulum of megakaryoblasts can distinquish these cells from myeloblasts on electron microscope examination. This can also be accomplished by the use of monoclonal or polyclonal platelet-specific antibodies.

Figures 2 through 23 illustrate the great morphological diversity of the acute leukemias.